Predictors of later bipolar disorder in patients with subthreshold symptoms

Introduction: The clinical significance of subthreshold bipolar disorder (SBD), which is characterized by an insufficient number or severity of hypomanic symptoms to qualify for a formal bipolar disorder diagnosis, remains to be determined. Methods: We examined the outcomes three years later (2004-2005; Wave 2) of 40,512 civilian, non-institutionalized subjects who endorsed elation and/or irritability but did not meet full criteria for lifetime mania or hypomania in 2001-2002 (Wave 1). Results: The likelihood of developing a clear episode of mania or hypomania by Wave 2 was significantly increased in subjects with elation or only irritability at Wave 1 compared with subjects who did not endorse either (OR 2.8, p<0.01 for each). Endorsement of both symptoms at Wave 1 increased the likelihood of a new episode of mania or hypomania 4.6 times, which was significantly higher than for those with only elation or irritability (p<.05 for each). Limitations: SBD was not limited to depression, reducing comparability to previous studies. Despite the large sample size, there were not enough subjects to determine the impact of different numbers and types of additional symptoms on bipolar outcome. Although the majority of subjects were followed between the two Waves, the total duration of follow-up was probably too short to determine the long-term conversion rate to mania or hypomania. Conclusions: Elation and/or irritability, especially if accompanied by trouble concentrating, racing thoughts or hyperactivity, may represent a prodrome of formal bipolar disorder that indicate close follow-up and cautious use of antidepressants.